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Background: Pulmonary metastasectomy (PM) is the most frequently performed local ablative therapy for leiomyosarcoma (LMS), synovial sarcoma (SyS), and undifferentiated pleomorphic sarcoma (UPS). This study aimed to assess surgical feasibility, outcome, and clinical prognostic factors, as well as the value of a peri-interventional systemic therapy.
Methods: This multicenter retrospective study enrolled 77 patients with LMS, SyS, or UPS who underwent first-time complete resection of isolated lung metastases between 2009 and 2021. Disease-free survival (DFS), overall survival (OS), and clinical prognostic factors were analyzed.
Results: After the first PM, the median DFS was 7.4 months, and the median OS was 58.7 months. A maximal lesion diameter greater than 2 cm was associated with reduced DFS in both the univariable (hazard ratio [HR], 2.29; p = 0.006) and multivariable (HR, 2.60; p = 0.005) analyses. The univariable analysis identified a maximal lesion diameter greater than 2 cm as an adverse prognostic factor for OS (HR, 5.6; p < 0.001), whereas a treatment-free interval longer than 12 months was associated with improved OS (HR, 0.42; p = 0.032). The addition of systemic therapy was associated with a trend toward improved DFS for patients with lesions larger than 2 cm (HR, 0.29; p = 0.063). Severe postoperative complications (grade ≥IIIa) occurred in 2 % of the patients.
Conclusion: The size of resected lung metastases might be a more relevant prognostic factor than their number for patients with LMS, SyS, or UPS. For patients with lung metastases larger than 2 cm in maximal diameter, additional systemic therapy may be warranted.
Donor age is one factor to optimize allogeneic hematopoietic cell transplantation (alloHCT). Therefore, we investigated whether young unrelated donors (UD) provide a benefit for older patients with myeloid malignancies compared to HLA-identical sibling donors (MSD). We performed a retrospective registry study on patients ≥50 years who received a first alloHCT between 2010 and 2020. We compared event-free survival (EFS) of patients who were transplanted from MSD aged ≥50 years versus UD aged ≤35 years who were HLA-compatible for HLA-A, -B, -C, and -DRB1. In total, we analyzed data from 3460 patients. With multivariable adjustment EFS (HR 0.86, p = 0.003), OS (HR 0.82, p < 0.001), and risk of relapse (HR 0.84, p = 0.018) were significantly better for HLA-compatible UD compared to MSD. No survival advantage was found, when UD with unfavorable sex or CMV constellation were compared to MSD with favorable constellations. In a meta-analysis on 9905 patients with myeloid malignancies, including ours, we found reduced risk of relapse (pooled HR 0.78, p = 0.006) and better EFS (pooled HR 0.89, p < 0.001) for young matched UD versus MSD. To select young HLA-compatible UD over older MSD may reduce relapse risk and improve survival for older patients with myeloid malignancies.
Background
Local ablative therapies (LAT) are increasingly used in patients with metastatic soft tissue sarcoma (STS), yet evidence-based standards are lacking. This study aimed to assess the impact of LAT on survival of metastatic STS patients and to identify prognostic factors.
Methods
In this retrospective multicenter study, 246 STS patients with metastatic disease who underwent LAT on tumor board recommendation between 2017 and 2021 were analyzed. A mixed effects model was applied to evaluate multiple survival events per patient.
Results
Median overall survival (OS) after first metastasis was 5.4 years with 1-, 2- and 5-year survival rates of 93.7, 81.7, and 53.1%, respectively. A treatment-free interval ≥12 months and treatment of liver metastases were positively correlated with progression-free survival (PFS) after LAT (HR=0.61, p=0.00032 and HR=0.52, p=0.0081, respectively). A treatment-free interval ≥12 months and treatment of metastatic lesions in a single organ site other than lung and liver were positive prognostic factors for OS after first LAT (HR=0.50, p=0.028 and HR=0.40, p=0.026, respectively) while rare histotypes and LAT other than surgery and radiotherapy were negatively associated with OS after first LAT (HR=2.56, p=0.020 and HR=3.87, p=0.025). Additional systemic therapy was independently associated with a PFS benefit in patients ≤60 years with ≥4 metastatic lesions (for max. diameter of treated lesions ≤2cm: HR=0.32, p=0.02 and >2cm: HR=0.20, p=0.0011, respectively).
Conclusion
This multicenter study conducted at six German university hospitals underlines the value of LAT in metastatic STS. The exceptionally high survival rates are likely to be associated with patient selection and treatment in specialized sarcoma centers.
Introduction: Chimeric antigen receptor positive T cell (CAR-T cell) treatment became standard therapy for relapsed or refractory hematologic malignancies, such as non-Hodgkin’s lymphoma and multiple myeloma. Owing to the rapidly progressing field of CAR-T cell therapy and the lack of generally accepted treatment guidelines, we hypothesized significant differences between centers in the prevention, diagnosis, and management of short- and long-term complications. Methods: To capture the current CAR-T cell management among German centers to determine the medical need and specific areas for future clinical research, the DAG-HSZT (Deutsche Arbeitsgemeinschaft für Hämatopoetische Stammzelltransplantation und Zelluläre Therapie; German Working Group for Hematopoietic Stem Cell Transplantation and Cellular Therapy) performed a survey among 26 German CAR-T cell centers. Results: We received answers from 17 centers (65%). The survey documents the relevance of evidence in the CAR-T cell field with a homogeneity of practice in areas with existing clinical evidence. In contrast, in areas with no – or low quality – clinical evidence, we identified significant variety in management in between the centers: management of cytokine release syndrome, immune effector cell-related neurotoxicity syndrome, IgG substitution, autologous stem cell backups, anti-infective prophylaxis, and vaccinations. Conclusion: The results indicate the urgent need for better harmonization of supportive care in CAR-T cell therapies including clinical research to improve clinical outcome.
Background
Whether high-dose cytarabine-based salvage chemotherapy, administered to induce complete remission in patients with poor responsive or relapsed acute myeloid leukaemia scheduled for allogeneic haematopoietic stem-cell transplantation (HSCT) after intensive conditioning confers a survival advantage, is unclear.
Methods
To test salvage chemotherapy before allogeneic HSCT, patients aged between 18 and 75 years with non-favourable-risk acute myeloid leukaemia not in complete remission after first induction or untreated first relapse were randomly assigned 1:1 to remission induction with high-dose cytarabine (3 g/m2 intravenously, 1 g/m2 intravenously for patients >60 years or with a substantial comorbidity) twice daily on days 1–3 plus mitoxantrone (10 mg/m2 intravenously) on days 3–5 or immediate allogeneic HSCT for the disease control group. Block randomisation with variable block lengths was used and patients were stratified by age, acute myeloid leukaemia risk, and disease status. The study was open label. The primary endpoint was treatment success, defined as complete remission on day 56 after allogeneic HSCT, with the aim to show non-inferiority for disease control compared with remission induction with a non-inferiority-margin of 5% and one-sided type 1 error of 2·5%. The primary endpoint was analysed in both the intention-to-treat (ITT) population and in the per-protocol population. The trial is completed and was registered at ClinicalTrials.gov, NCT02461537.
Findings
281 patients were enrolled between Sept 17, 2015, and Jan 12, 2022. Of 140 patients randomly assigned to disease control, 135 (96%) proceeded to allogeneic HSCT, 97 (69%) after watchful waiting only. Of 141 patients randomly assigned to remission induction, 134 (95%) received salvage chemotherapy and 128 (91%) patients subsequently proceeded to allogeneic HSCT. In the ITT population, treatment success was observed in 116 (83%) of 140 patients in the disease control group versus 112 (79%) of 141 patients with remission induction (test for non-inferiority, p=0·036). Among per-protocol treated patients, treatment success was observed in 116 (84%) of 138 patients with disease control versus 109 (81%) of 134 patients in the remission induction group (test for non-inferiority, p=0·047). The difference in treatment success between disease control and remission induction was estimated as 3·4% (95% CI –5·8 to 12·6) for the ITT population and 2·7% (–6·3 to 11·8) for the per-protocol population. Fewer patients with disease control compared with remission induction had non-haematological adverse events grade 3 or worse (30 [21%] of 140 patients vs 86 [61%] of 141 patients, χ2 test p<0·0001). Between randomisation and the start of conditioning, with disease control two patients died from progressive acute myeloid leukaemia and zero from treatment-related complications, and with remission induction two patients died from progressive acute myeloid leukaemia and two from treatment-related complications. Between randomisation and allogeneic HSCT, patients with disease control spent a median of 27 days less in hospital than those with remission induction, ie, the median time in hospital was 15 days (range 7–64) versus 42 days (27–121, U test p<0·0001), respectively.
Interpretation
Non-inferiority of disease control could not be shown at the 2·5% significance level. The rate of treatment success was also not statistically better for patients with remission induction. Watchful waiting and immediate transplantation could be an alternative for fit patients with poor response or relapsed acute myeloid leukaemia who have a stem cell donor available. More randomised controlled intention-to-transplant trials are needed to define the optimal treatment before transplantation for patients with active acute myeloid leukaemia.
In emergency medicine, timely intervention for patients at risk of suicide is often hindered by delayed access to specialised psychiatric care. To bridge this gap, we introduce a speech-based approach for automatic suicide risk assessment. Our study involves a novel dataset comprising speech recordings of 20 patients who read neutral texts. We extract four speech representations encompassing interpretable and deep features. Further, we explore the impact of gender-based modelling and phrase-level normalisation. By applying gender-exclusive modelling, features extracted from an emotion fine-tuned wav2vec2.0 model can be utilised to discriminate high- from low suicide risk with a balanced accuracy of 81%. Finally, our analysis reveals a discrepancy in the relationship of speech characteristics and suicide risk between female and male subjects. For men in our dataset, suicide risk increases together with agitation while voice characteristics of female subjects point the other way.
Background
Emotions play a key role in psychotherapy. However, a problem with examining emotional states via self-report questionnaires is that the assessment usually takes place after the actual emotion has been experienced which might lead to biases and continuous human ratings are time and cost intensive. Using the AI-based software package Non-Verbal Behavior Analyzer (NOVA), video-based emotion recognition of arousal and valence can be applied in naturalistic psychotherapeutic settings. In this study, four emotion recognition models (ERM) each based on specific feature sets (facial: OpenFace, OpenFace-Aureg; body: OpenPose-Activation, OpenPose-Energy) were developed and compared in their ability to predict arousal and valence scores correlated to PANAS emotion scores and processes of change (interpersonal experience, coping experience, affective experience) as well as symptoms (depression and anxiety in HSCL-11).
Materials and methods
A total of 183 patient therapy videos were divided into a training sample (55 patients), a test sample (50 patients), and a holdout sample (78 patients). The best ERM was selected for further analyses. Then, ERM based arousal and valence scores were correlated with patient and therapist estimates of emotions and processes of change. Furthermore, using regression models arousal and valence were examined as predictors of symptom severity in depression and anxiety.
Results
The ERM based on OpenFace produced the best agreement to the human coder rating. Arousal and valence correlated significantly with therapists’ ratings of sadness, shame, anxiety, and relaxation, but not with the patient ratings of their own emotions. Furthermore, a significant negative correlation indicates that negative valence was associated with higher affective experience. Negative valence was found to significantly predict higher anxiety but not depression scores.
Conclusion
This study shows that emotion recognition with NOVA can be used to generate ERMs associated with patient emotions, affective experiences and symptoms. Nevertheless, limitations were obvious. It seems necessary to improve the ERMs using larger databases of sessions and the validity of ERMs needs to be further investigated in different samples and different applications. Furthermore, future research should take ERMs to identify emotional synchrony between patient and therapists into account.
Remote sensing (RS) enables a cost-effective, extensive, continuous and standardized monitoring of traits and trait variations of geomorphology and its processes, from the local to the continental scale. To implement and better understand RS techniques and the spectral indicators derived from them in the monitoring of geomorphology, this paper presents a new perspective for the definition and recording of five characteristics of geomorphodiversity with RS, namely: geomorphic genesis diversity, geomorphic trait diversity, geomorphic structural diversity, geomorphic taxonomic diversity, and geomorphic functional diversity. In this respect, geomorphic trait diversity is the cornerstone and is essential for recording the other four characteristics using RS technologies. All five characteristics are discussed in detail in this paper and reinforced with numerous examples from various RS technologies. Methods for classifying the five characteristics of geomorphodiversity using RS, as well as the constraints of monitoring the diversity of geomorphology using RS, are discussed. RS-aided techniques that can be used for monitoring geomorphodiversity in regimes with changing land-use intensity are presented. Further, new approaches of geomorphic traits that enable the monitoring of geomorphodiversity through the valorisation of RS data from multiple missions are discussed as well as the ecosystem integrity approach. Likewise, the approach of monitoring the five characteristics of geomorphodiversity recording with RS is discussed, as are existing approaches for recording spectral geomorhic traits/ trait variation approach and indicators, along with approaches for assessing geomorphodiversity. It is shown that there is no comparable approach with which to define and record the five characteristics of geomorphodiversity using only RS data in the literature. Finally, the importance of the digitization process and the use of data science for research in the field of geomorphology in the 21st century is elucidated and discussed.
